A series of integrated clinical and basic pharmacological investigations are proposed to study systematically the anticonvulsant activity, metabolism, toxicity and tolerance of selected barbiturate derivatives: (A) Clinical and laboratory studies with C14-labelled primidone (the 2-desoxy-derivative of phenobarbital) will extend and refine our previous investigations with this compound; (B) a series of laboratory studies with selected 2-desoxy-derivatives of anticonvulsant barbiturates other than phenobarbital will establish the specificity of this molecular alteration of the barbiturate molecule in the enhancement of anticonvulsant activity and the reduction of toxicity; (C) a series of clinical and laboratory studies with the dimethoxymethyl derivative of phenobarbital will be conducted in conjunction with on-going clinical trials of this drug to provide pharmacokinetic data correlated with studies of efficacy and toxicity of this compound which is essential information for the rational clinical utilization of an anticonvulsant drug. Analytical techniques will include gas-liquid and thin-layer chromatography, liquid scintillation counting, electroencephalography and correlation of clinical control and toxicity with drug metabolism. An important ancillary accomplishment of these investigations will be the establishment of a coordinated group of investigators in the clinical and basic science aspects of the neuropharmacology of epilepsy.